Recent figures confirm a continuous rise in rates of overweight and obesity. Since the 1980s, the prevalence of both conditions has more than doubled worldwide. In 2014, more than half of the adult population was tackling weight issues, with 13% living with obesity and 39% being overweight. Even more alarming are the data concerning children; in 2014, 40 million children under the age of 5 years were either overweight or obese. The big question is: What is the pharmaceutical industry doing to help tackle this epidemic?
A new understanding of obesity
While excessive intake of high-energy foods in conjunction with reduced physical activity is the classic cause of obesity, associations with exposure to some endocrine disruptors (chemicals that interfere with hormonal balances) have also been put forward as potential causes. New insights such as this have provided pharma with some promising ways forward in the development of drugs to help people contending with weight issues and any associated impact to health and well-being.
“From a therapeutic perspective, obesity is essentially a new field,” says Alan Moses, chief medical officer at Novo Nordisk. “There is a lot of groundwork that needs to be done to build appreciation of the fact that obesity should be seen as a disease – and medical organizations are certainly recognizing this because of its consequences. It is not being overweight per se that is the issue; it is the co-morbidities that so adversely impact the lives of the individuals that are affected.” Indeed, obesity is often associated with type 2 diabetes, cardiovascular disease, osteoarthritis, low-degree inflammation, immune disturbances, endocrine complications, and sleep apnoea. Even some types of cancer have been associated with a pre-existing obese condition. All of these disorders necessitate specific medications or treatments.
The pharmacological approach to treating obesity
An increasing understanding of obesity has highlighted that long-term weight control cannot always be achieved through diet and exercise alone. “From our research with patients, we know they can be motivated and committed to losing weight but often feel a lack of control over hunger and cravings,” shares Tom Cannell, chief operating officer and president of global commercial products at Orexigen Therapeutics. “Weight loss is complex and for many people, diet and exercise alone may not be enough.”
In such cases, a pharmacological approach provides a non-surgical strategy to treat obesity and improve health. Drugs that are currently approved and marketed both in the European Union and the USA for long-term obesity management tend to target calorie reduction. For example, orlistat, marketed by Roche as Xenical and approved by the Food and Drug Administration and European Medicines Agency in the late 1990s, is a pancreatic lipase inhibitor that lowers fat absorption, and hence also lowers calorie intake.
Two, more recently approved drugs, target appetite – Contrave (naltrexone HCI/bupropion HCI), developed by Orexigen Therapeutics, and liraglutide (NN2211) (commercially available as Saxenda), developed by Novo Nordisk.
Contrave is believed to work on two important areas of the brain – the hypothalamus (the hunger center) to reduce hunger and the mesolimbic reward system to help control cravings. Liraglutide, on the other hand, is a glucagon-like protein-1 (GLP-1) receptor agonist and originally developed by Novo Nordisk as a compound against type 2 diabetes. It was later approved for the treatment of obesity in people without diabetes. GLP-1 receptor agonists are modified normal human peptides, applied in a way that they are present at higher levels in the blood than can be achieved under normal circumstances, and last longer than the normal human peptides. This leads to larger exposure to physiologically active peptides that reside in the gastrointestinal tract and that act on pancreatic beta cells to modulate the secretion of insulin, and on alpha cells to suppress glucagon. The drug also acts on the central nervous system and brain (specifically the hypothalamus) to affect appetite.
Integrated therapies and education
Many of these pharmacological therapies have been approved in combination with lifestyle interventions. Indeed, an integrated approach that includes patient and public education seems necessary to tackle this global health issue. “We do not believe that medication alone is the solution to overweight and obesity,” says Dr Moses. “A plan for the improvement of lifestyle, including exercise and the control of calories consumed needs to be made. The drugs can, however, be a very important help.”
Dr Cannell of Orexigen Therapeutics agrees, saying: “As a patient-centered organization, we recognize that patients often experience emotions that hinder them from losing weight and keeping it off. They describe feeling trapped in an ongoing weight loss struggle of ups and downs that can be filled with emotions like frustration and sometimes failure. We want to empower patients with the knowledge and tools that can help them overcome these barriers. We start with educating patients on the role of the brain in weight loss and explain how Contrave may help.”
As part of these efforts to empower patients, Orexigen has created a 360-degree educational campaign called ‘Brains behind Weight Loss,’ which helps patients via TV, print, and social media as well as provides support tools via the website. “We believe this campaign can help patients and healthcare providers have engaging and motivating discussions, by changing the conversation from why you should lose weight to why you struggle to lose weight. This important shift may help alleviate frustration for patients, which can help them stay motivated and committed to a complete weight loss regimen,” shares Dr Cannell.
Novo Nordisk is involved in similar education campaigns, including public education through a program called ‘Cities Changing Diabetes. Here, the focus is on prevention rather than treatment, as well as on the determinants of developing diabetes – of which obesity is a key component. “The best treatment is no treatment because the disease was prevented,” says Dr Moses, “but it is a very difficult challenge, because there are so many influences that push us in the wrong direction.” Mexico City, Houston, Copenhagen, Shanghai, Tianjin, Johannesburg and Vancouver, are partners of the programme.
The future of obesity treatment
The increasing acknowledgment of obesity as a disease, along with more patient-centered views on care, are leading to integrated approaches that combine lifestyle interventions with pharmacological treatments. Novo Nordisk and Orexigen Therapeutics are two key players in helping ease the burden of a condition that severely impacts quality of life and healthcare spending. And they look set to remain key players. “New drugs are in the pipeline and are in Phase II clinical trials,” shares Novo Nordisk’s Dr Moses. “One of these compounds is semaglutide, which acts in a way that is similar to Saxenda, but based on clinical trials for diabetes seems more efficacious.”
For Orexigen’s Dr Cannell, “A true personalized medicine approach may be a path in the future. From our perspective, successful management of weight loss and obesity involves developing the treatment strategy that is going to work for the individual patient. This starts with understanding the patient’s struggle with weight loss, their emotional state, and their motivation for losing weight.”
Over all, the future looks promising for obesity treatment and pharma companies are certainly doing their bit – but developments can’t come too soon. As emphasised by Dr Cannell: “With over 25% of the US population struggling with obesity, we need effective treatment regimens today.”